The effect of X-linked dosage compensation on complex trait variation.
Where this comes from
- Record sourced from PubMed, PMID 31285442.
- Also identified by DOI 10.1038/s41467-019-10598-y and PMC identifier 6614401.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Quantitative genetics theory predicts that X-chromosome dosage compensation (DC) will have a detectable effect on the amount of genetic and therefore phenotypic trait variances at associated loci in males and females. Here, we systematically examine the role of DC in humans in 20 complex traits in a sample of more than 450,000 individuals from the UK Biobank and 1600 gene expression traits from a sample of 2000 individuals as well as across-tissue gene expression from the GTEx resource. We find approximately twice as much X-linked genetic variation across the UK Biobank traits in males (mean h<sup>2</sup><sub>SNP</sub> = 0.63%) compared to females (mean h<sup>2</sup><sub>SNP</sub> = 0.30%), confirming the predicted DC effect. Our DC estimates for complex traits and gene expression are consistent with a small proportion of genes escaping X-inactivation in a trait- and tissue-dependent manner. Finally, we highlight examples of biologically relevant X-linked heterogeneity between the sexes that bias DC estimates if unaccounted for.
Medical subject headings
- Genes, X-Linked
- Genetic Loci
- Genetic Variation
- Multifactorial Inheritance
- X Chromosome Inactivation